Density functional theory (B3LYP) and ab initio (MP2) methods with the 6-31G(d,p) basis set are used to study the mechanisms for the hydrolysis of N-(2-oxo-1,2-dihydro-pyrimidinyl) formamide (PFA) in the gas phase. The direct and the water-assisted hydrolysis processes are considered, involving one and two water molecules, respectively. Three different pathways are explored in each case. In the first pathway, the O atom of water first attacks at the C atom of amide while one H atom of water transfers toward the oxygen of amide, leading to an intermediate of tetrahedral coordinated carbon with two OH groups. In the subsequent step, the hydroxyl H atom transfers to the N atom of pyrimidine ring and the C-N covalent bond of amide dissociates simultaneously. In the second path, the O and one H of water attack at the C of amide and the N of pyrimidine ring, respectively, while the C-N bond of amide dissociates. In the third path, three processes occur simultaneously: the O of water attacks at the C of amide, one H atom attacks at the N of amide, and the C-N bond of amide is broken. It is shown that the second pathway is favored for the direct hydrolysis while the first pathway is favored for the water-assisted hydrolysis. It is also shown that the water-assisted hydrolysis is slightly more favorable than the direct hydrolysis. Moreover, solvent effects on five pathways are evaluated with Monte Carlo simulation (MC) and free energy perturbation methods. It is shown that the solvent water slightly reduces the energy barrier in each pathway. The first pathway in the water-assisted hydrolysis remains the most favorable when the solvent effects of bulk water are taken into account.